A Study of CC-122 to Assess the Safety and Tolerability i... | NCT02509039

Status Module

Label	Type	Description	Intervention Names
CC-122	Experimental	CC-122 is administered orally, on a 5 continuous days out of 7 days per week intermittent dosing schedule.	Drug: CC-122

Name	Type	Description	Arm Group Labels	Other Names
CC-122	Drug	5 continuous days out of 7 days per week intermittent dosing	CC-122

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants With Dose-Limiting Toxicities (DLTs)	NCI CTCAE Version 4.03 will be used to grade adverse events. Events described below will be classified as DLTs: Non-hematologic AEs: Suspected to be related to CC-122, commences during the DLT evaluation period, and is ≥ Grade 3 Laboratory abnormalities: Suspected to be related to CC-122, commences during the DLT evaluation period, and is ≥ Grade 3 Hematologic: Any febrile neutropenia, Grade 4 neutropenia lasting > 7 days, Grade 4 thrombocytopenia lasting > 24 hours or thrombocytopenia of any grade requiring platelet transfusions, Any Grade 3/4 thrombocytopenia with clinically significant bleeding Hepatic: Grade 4 liver function tests or Grade 3 ALT with Grade 2 or higher bilirubin will be considered a DLT, irrespective of underlying attribution. Other Grade 3 LFTs due to disease progression in the liver will not be considered DLTs Other adverse events: Suspected to be related to CC-122 and necessitating a dose reduction during the DLT evaluation period	From first dose up to at least 28 days (Cycle 1)
Maximum Tolerated Dose (MTD)	The MTD is defined as the last dose level below the non-tolerated dose (NTD) with zero or one out of six evaluable participants experiencing dose-limiting toxicities (DLTs) during the DLT evaluation period. At least 6 participants will be enrolled at the MTD/recommended phase 2 dose (RP2D). MTD will be evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria Version 4.03	From first dose up to at least 28 days (Cycle 1)
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	An adverse event is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study, using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria version 4.03	From first dose to 28 days post last dose of investigational product (Up to approximately 92 months)
Pharmacokinetic Parameters of CC-122: AUC0-t

Secondary Outcomes

Measure	Description	Time Frame
Best Overall Response (BOR)	BOR by investigator is defined according to International Working Group (IWG) Revised Response Criteria for Malignant Lymphoma for NHL patients and Response Evaluation Criteria in Solid Tumors (RECIST 1.1) for solid tumors patients. For NHL, complete remission (CR)=disappearance of all evidence of disease. Partial response (PR)=regression of measurable disease and no new sites. Stable disease (SD)=failure to attain CR/PR or PD. Progressive disease (PD)=any new lesion or increase by >=50% of previously sites from nadir. For solid tumors, complete response (CR)=disappearance of all target and non-target lesions and no new lesions. PR=at least a 30% decrease in the sum of diameters of target lesions and no new lesions. SD=neither sufficient shrinkage to qualify for PR or increase to qualify for PD. PD=at least 20% increase in the sum of diameters of target lesions from nadir.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Understand and voluntarily sign an informed consent document prior to any study-related assessments/procedures are conducted
20 years or older, with histological or cytological confirmation of advanced solid tumors or Non-Hodgkin's Lymphoma (NHL), including those who have progressed on standard anticancer therapy or for whom no other conventional therapy exists
Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2 for all tumors
Subjects must have the following laboratory values:

・Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L
- Hemoglobin (Hgb) ≥ 9 g/dL, drawn at least 7 days after the last RBC transfusion
- Platelets (Plt) ≥ 100 x 109/L, drawn at least 7 days after the last platelet transfusion
- Potassium within normal limits or correctable with supplements
- Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 3 x upper limit of normal (ULN) or ≤ 5.0 x ULN if liver tumors are present
- Serum bilirubin ≤ 1.5 x ULN; subjects with serum bilirubin >1.5 x ULN and ≤ 2 x ULN may be enrolled if agreed to by the sponsor
- Serum creatinine ≤ ULN or 24-hour clearance ≥ 50 mL/min
- Negative serum pregnancy test in females of childbearing potential as per the CC-122 Pregnancy Prevention Rist Management Plan
Able to adhere to the study visit schedule and other protocol requirements
Must adhere to the Pregnancy Prevention Rist Management Plan

Exclusion Criteria:

Subjects with primary central nervous system (CNS) malignancies or symptomatic central nervous system metastases. Subjects with brain metastases that have been previously treated and are stable for 6 weeks are allowed
Known acute or chronic pancreatitis
Any peripheral neuropathy ≥ NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) Grade 2
Persistent diarrhea or malabsorption ≥ NCI CTCAE Grade 2, despite medical management
Impaired cardiac function or clinically significant cardiac diseases, including any of the following:
- Left Ventricular Ejection Fraction (LVEF) < 45% as determined by Multiple Gated Acquisition Scan (MUGA) scan or Echocardiogram (ECHO)
- Complete left bundle branch, or bifascicular block
  - Congenital long QT syndrome
  - Persistent or uncontrolled ventricular arrhythmias or atrial fibrillation
  - QTcF > 460 msec on screening electrocardiogram (ECG) (mean of triplicate recordings)
  - Unstable angina pectoris or myocardial infarction ≤ 3 months prior to starting CC-122
  - Troponin-T value >0.4 ng/mL or Brain Natriuretic Peptide (BNP) >300 pg/mL Subjects with baseline troponin-T >ULN or BNP >100 pg/mL are eligible but must and optimization of cardioprotective therapy.
- Other clinically significant heart disease such as congestive heart failure requiring treatment or uncontrolled hypertension (blood pressure ≥ 160/95 mmHg)
Prior systemic cancer-directed treatments or investigational modalities ≤ 5 half lives or 4 weeks, whichever is shorter, prior to starting CC-122 or who have not recovered from side effects of such therapy. Luteinizing hormone-releasing hormone (LHRH) agonists will be allowed for subjects with metastatic prostate cancer
Major surgery ≤ 2 weeks prior to starting CC-122 or still recovering from post operative side effects
Women who are pregnant or breast feeding. Adults of reproductive potential not employing two forms of birth control as per Pregnancy Prevention Risk Management Plan (PPRMP)
Known human immunodeficiency virus (HIV) infection
Known acute or chronic hepatitis B or C virus infection
Status post solid organ transplant
Less than 100 days for subjects receiving autologous hematologic stem cell transplant (HSCT); or 6 months for subjects receiving allogeneic HSCT, or if otherwise not fully recovered from HSCT-related toxicity

a. The 6-month exclusionary period for recovery from HSCT-associated toxicity, applies regardless of whether an autologous or allogeneic transplant was performed
Known hypersensitivity to any component of the formulation of CC-122
Any significant medical condition (including active or controlled infection or renal disease), laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study
Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study
Any condition that confounds the ability to interpret data from the study

Name	Affiliation	Role
Bristol-Myers Squibb	Bristol-Myers Squibb	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Local Institution - 002		Koto-ku	Tokyo	1358550	Japan
Local Institution - 003

Label	URL
BMS Clinical Trial Information	View source
BMS Clinical Trial Patient Recruiting	View source

ID	Title	Description
FG000	AIC 2.0 mg	CC-122 administered orally at a dose of 2.0 mg on a 5 continuous days out of 7 days per week intermittent dosing schedule using active ingredient in capsule (AIC)
FG001	AIC 3.0 mg	CC-122 administered orally at a dose of 3.0 mg on a 5 continuous days out of 7 days per week intermittent dosing schedule using active ingredient in capsule (AIC)
FG002	AIC 4.0 mg	CC-122 administered orally at a dose of 4.0 mg on a 5 continuous days out of 7 days per week intermittent dosing schedule using active ingredient in capsule (AIC)
FG003	F6 3.0 mg	CC-122 administered orally at a dose of 3.0 mg on a 5 continuous days out of 7 days per week intermittent dosing schedule using formulated capsules (F6)

ID	Title	Description
BG000	AIC 2.0 mg	CC-122 administered orally at a dose of 2.0 mg on a 5 continuous days out of 7 days per week intermittent dosing schedule using active ingredient in capsule (AIC)
BG001	AIC 3.0 mg

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Participants With Dose-Limiting Toxicities (DLTs)

NCI CTCAE Version 4.03 will be used to grade adverse events. Events described below will be classified as DLTs:

Non-hematologic AEs: Suspected to be related to CC-122, commences during the DLT evaluation period, and is ≥ Grade 3
Laboratory abnormalities: Suspected to be related to CC-122, commences during the DLT evaluation period, and is ≥ Grade 3
Hematologic: Any febrile neutropenia, Grade 4 neutropenia lasting > 7 days, Grade 4 thrombocytopenia lasting > 24 hours or thrombocytopenia of any grade requiring platelet transfusions, Any Grade 3/4 thrombocytopenia with clinically significant bleeding
Hepatic: Grade 4 liver function tests or Grade 3 ALT with Grade 2 or higher bilirubin will be considered a DLT, irrespective of underlying attribution. Other Grade 3 LFTs due to disease progression in the liver will not be considered DLTs
Other adverse events: Suspected to be related to CC-122 and necessitating a dose reduction during the DLT evaluation period

All treated participants

Posted

Count of Participants

Participants

From first dose up to at least 28 days (Cycle 1)

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	AIC 2.0 mg	CC-122 administered orally at a dose of 2.0 mg on a 5 continuous days out of 7 days per week intermittent dosing schedule using active ingredient in capsule (AIC)

ID	Term
D008223	Lymphoma
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D008232	Lymphoproliferative Disorders

OG000	AIC 2.0 mg	CC-122 administered orally at a dose of 2.0 mg on a 5 continuous days out of 7 days per week intermittent dosing schedule using active ingredient in capsule (AIC)
OG001	AIC 3.0 mg	CC-122 administered orally at a dose of 3.0 mg on a 5 continuous days out of 7 days per week intermittent dosing schedule using active ingredient in capsule (AIC)
OG002	AIC 4.0 mg	CC-122 administered orally at a dose of 4.0 mg on a 5 continuous days out of 7 days per week intermittent dosing schedule using active ingredient in capsule (AIC)
OG003	F6 3.0 mg	CC-122 administered orally at a dose of 3.0 mg on a 5 continuous days out of 7 days per week intermittent dosing schedule using formulated capsules (F6)